Dr. Bushman’s Lab

Dr. Bushman’s laboratory group studies molecular signaling in the mesenchymal-epithelial interactions of prostate development and reactivation of embryonic signaling pathways in prostatic neoplasia. The laboratory (K6-560/562) and offices (K6-561) are located in the Cancer Center of the UW Hospitals and Clinics.

Work in my laboratory is focused on the regulation of growth during normal prostate development and the reactivation of developmental pathways in prostatic neoplasia. Working in the mouse, we are examining the role of the Sonic hedgehog (Shh) signaling pathway and Bone Morphogenetic Protein –4 (BMP-4) in the mesenchymal-epithelial signaling that regulates prostate ductal budding. In addition, we are studying the role of the different Gli genes in the transcriptional response to Shh signaling and examining the activities of the plant alkaloid cyclopamine on Shh signaling, target gene activation, and growth of the developing prostate.

We have recently found that Shh signaling is up-regulated in prostate cancer. Using a xenograft tumor model, we have shown that activation of Shh signaling increases stromal Gli gene expression and – by a paracrine mechanism – significantly accelerates tumor growth. These observations suggest that the Shh pathway may be a critically important pathway in the regulation of tumor growth and may provide a mechanism by which tumor cells recruit the host stromal cells to support tumor growth.

Ongoing work in our laboratory includes efforts to understand the environmental exposures, including dietary exposures, that may activate prostate Shh signaling and create conditions that favor tumor progression.